P14 OCULAR TOXICITY IN TRANSPLANT INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH BELANTAMAB MAFODOTIN, LENALIDOMIDE AND DEXAMETHASONE IN A PHASE 1/2 TRIAL
Authors: I. Ntanasis-Stathopoulos, M. Gavriatopoulou, P. Malandrakis, D. Fotiou, N. Kanellias, M. Migkou, F. Theodorakakou, V. Spiliopoulou, R. Syrigou, E. Eleutherakis-Papaiakovou, S. Gkolfinopoulos, K. Manousou, E. Kastritis, M.A. Dimopoulos, E. Terpos
Journal: HemaSphere (2023)

Introduction: Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. Corneal examination findings (e.g., keratopathy) and visual acuity changes are common with belamaf, warranting belamaf dose modifications (dose reduction, dose holds) or treatment discontinuation. Here, we evaluate the ocular adverse effects of belamaf and their impact on daily functioning in pts participating in the phase 1/2 BelaRd study. Methods: The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 adult pts with TI NDMM. In Part 1 of the study (dose selection), 18 pts are randomized (1:1:1) in 3 cohorts to receive belamaf 2.5, 1.9, or 1.4 mg/kg doses by intravenous infusion once every 8 weeks (Q8W) plus Rd and the safety/tolerability of the combination is evaluated for pts with ≥4 weeks of follow up. As a safety review found no unexpected findings, an additional 6 pts were enrolled in each dose cohort to select the belamaf recommended phase 2 dose (RP2D). Part 2 (dose expansion; not initiated) will further evaluate the safety and clinical activity of belamaf RP2D plus Rd. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events and dry eye disease severity and vision-related functioning is assessed with the patient-reported Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis included all Part 1 pts from the BelaRd study (data cut-off: 24 June 2022). Results: Thirty-six pts were included in this analysis, who were followed up for a median of 9.5 months (range 3.2–15.4). At baseline (cycle 1 day 1), all pts had ocular comorbidities. During follow-up, the most common any grade (gr) ocular adverse events (OAEs) across cohorts were dry eye and visual acuity reduced (Table 1). Gr 3 OAEs were observed only for visual acuity reduced, visual impairment, and cataract; no Gr 4 OAEs were observed. Belamaf doses skipped due to OAEs per the total number of planned belamaf administrations were 23/68 (33.8%), 15/73 (20.5%), and 10/69 (14.5%) in cohorts 2.5, 1.9, and 1.4 mg/kg, respectively. For the entire pt population, median times to resolution of keratopathy and BCVA change from baseline were 2.1 months (range 0.7–11.1) and 2.0 months (range 0.3–6.9), respectively; across cohorts, numerically similar median times to resolution were observed for each OAE (Table 1). Low (<2.0%) proportions of OSDI assessments included ‘all’ or ‘most of the time’ impact of study treatment on activities of daily living (ADLs), while most assessments were ‘some’ or ‘none of the time’. Table 1 - Most common ocular adverse events* by MedDRA preferred term and time to resolution Cohort2.5 mg/kg Cohort1.9 mg/kg Cohort1.4 mg/kg Patients, n 12 12 12 Most common OAEs † , n (%) Dry eye 11 (91.7) 12 (100.0) 12 (100.0) Visual acuity reduced 10 (83.3) 12 (100.0) 12 (100.0) Visual acuity reduced gr ≥3 4 (33.3) 2 (16.7) 6 (50.0) Keratopathy 8 (66.7) 11 (91.7) 9 (75.0) Visual impairment 8 (66.7) 9 (75.0) 10 (83.3) Visual impairment gr ≥3 1 (8.3) - - Vision blurred 7 (58.3) 7 (58.3) 7 (58.3) Foreign body in eye 6 (50.0) 6 (50.0) 9 (75.0) Time to resolution of OAEs † , months (median [range])^ Keratopathy 1.9 (0.7–11.1) 2.0 (0.9–9.2) 2.1 (1.0–4.6) Visual acuity reduced 2.1 (0.3–6.0) 2.1 (0.8–6.9) 1.8 (0.9–6.6) Ocular symptoms§ 1.7 (0.3–10.4) 1.1 (0.8–4.8) 1.1 (0.2–6.5) Dry eye 2.2 (0.9–4.6) 1.0 (0.9–3.9) 1.1 (0.3–6.5) Eye irritation 0.90 (0.8–1.0) 1.1 (1.0–1.1) 1.0 (0.3–1.8) Eye pain 0.9 (0.9–0.9) 0.9 (0.9–0.9) 0.6 (0.3–0.9) Foreign body in eye 1.8 (0.9–5.3) 1.8 (0.8–4.7) 1.3 (0.9–2.9) Lacrimation increased 1.3 (0.9–3.6) 0.9 (0.9–0.9) 0.9 (0.9–0.9) Vitreous floaters 2.1 (0.9–2.8) 2.9 (0.9–4.8) 3.2 (0.9–5.5) *Included OAEs were observed in ≥50.0% of the entire patient population. †OAEs are classified by MedDRA preferred term. ^Calculated over the total number of resolved events. §Median time to resolution shown only for ocular symptoms with ≥1 occurrenceBCVA, best corrected visual acuity; Gr, grade; MedDRA, Medical Dictionary for Regulatory Activities; n, number of patients; OAE, ocular adverse events Conclusions: No new ocular safety signals were observed with belamaf plus Rd in the upfront treatment of TI pts with NDMM; the observed eye toxicities were within the anticipated range with the use of belamaf. Keratopathy and BCVA change from baseline were resolved by a median of ~2 months; for each of these OAEs, similar times to resolution were recorded, across dose cohorts. Belamaf plus Rd had a minor impact on ADLs, especially in the 1.4 and 1.9 mg/kg doses.